Single-stranded RNA molecules can form secondary structures by folding back on themselves to form regions of local base-pairing. Several examples link elements of secondary structure to debilitating human conditions such as HIV or Alzheimer's disease. However, our understanding of its role in the evolution and function of a complete genome is limited at this time. We have preliminary evidence demonstrating that the genomes of several divergent organisms have evolved to preserve secondary structure in the coding regions of genes. The first aim of this proposal is to extend our analyses to a wide range of available genomes using computational methods, and to tie our findings to a biological function. We then plan to apply the methodology developed in AIM 1 to studying the effect of secondary structure on the regulation of alternative splicing. We hope to identify unique and important examples of secondary structure elements that affect splice site and branch site selection in human genes, and will further examine them using molecular biological techniques. [unreadable] [unreadable]